Ординатура / Офтальмология / Английские материалы / Diabetes and Ocular Disease Past, Present, and Future Therapies 2nd edition_Scott, Flynn, Smiddy_2009

14 Diabetes and Ocular Disease

risk factor for the development of retinopathy, as is the severity of the hyperglycemia. Hypertension is an additional risk factor, and optimal control of serum glucose and systemic blood pressure is of utmost importance in the management of patients with diabetes [3]. The natural history of diabetic retinopathy is progressive, and nearly all patients with type 1 and over 60% of patients with type 2 diabetes develop some degree of retinopathy over the course of 20 years [4]. The epidemiology of this disorder is discussed in detail in Chapter 5.

Visual morbidity and blindness can be combated effectively if treatment of retinopathy is instituted in a timely fashion. Landmark clinical trials, the Diabetic Retinopathy Study (DRS) and the Early Treatment Diabetic Retinopathy Study (ETDRS), demonstrated that effective treatment for retinopathy could reduce vision loss by 90% [4,5]. These studies underscored the critical need to have regular eye examinations so that patients are identified reliably at the time when laser photocoagulation is most effective. Timely detection and treatment of diabetic retinopathy could result in major reductions in health expenditures—savings that are quite cost-effective compared with other health care interventions [6].

The disparity between the availability of effective treatment and the continued increase in the number of patients with symptomatic diabetic retinopathy implies that there are barriers to optimal management of diabetic patients. Part of the problem lies in diabetic individuals not being aware of their need to have dilated eye evaluations. In addition, many individuals lack health insurance, sufficient funds, or a means of reaching a physician. Several studies have documented that many patients with diabetes do not receive regular dilated eye examinations, with most reporting that no more than 50% of individuals with diabetes receive an annual dilated eye examination [4]. An additional negative factor is the lack of coordination between the systemic care of patients with diabetes and their eye care. Frequently, there does not appear to be a systematic approach for feedback and communication between the primary care physician (who might be a diabetologist/endocrinologist, family physician, or internist), and the ophthalmologist or eye care provider. Thus, patients may not be referred or reminded to keep their appointment with their ophthalmologist, even when there have been significant findings on past eye examinations. Physicians managing patients with diabetes frequently do not understand the retinopathy scales, and results of eye examinations are commonly not reported to them.

An additional issue is the lack of patient access to appropriate care. On a global basis, the WHO reported that many patients were not receiving appropriate care because of a lack of public and professional awareness as well as an absence of treatment facilities [1]. In several developing countries, optimal care is inaccessible to the majority of the population [1].

This need to provide a framework for improved communication between and among nurses, primary care physicians, internists, endocrinologists, ophthalmologists, and other eye care providers is the key reason to develop a simplified classification system that can be employed on an international scale. A standard set of definitions of severity of diabetic retinopathy and macular edema is critical for communication among colleagues, and improved communication should lead to better patient care.

THE ETDRS AND ADDITIONAL CLASSIFICATIONS

OF DIABETIC RETINOPATHY

The ETDRS grading scale is based upon the modified Airlie House classification of diabetic retinopathy [5]. This scheme is based on seven standard 30-degree photographic fields that provide sufficient depth of field, adequate area, and magnification to provide an accurate representation of the status of the retina. A standard set of definitions and a standard set of photographs of various lesions describing the severity of retinopathy is employed (Table 2.1). The ETDRS grading scale continues to be applied widely in research settings, publications, and in meetings of retina subspecialty groups, for it has demonstrated satisfactory reproducibility and

Table 2.1. Abbreviated Summary of the Early Treatment Diabetic Retinopathy Study Scale of Diabetic Retinopathy Severity for Individual Eyes [5,7].

The scale grades the following abnormalities: hemorrhages (HE), microaneurysms (MA), hard exudates (HE), soft exudates (SE), intraretinal microvascular abnormalities (IRMA), venous beading (VB), new vessels < 1 disc diameter (DD) from the disc (NVD), new vessels elsewhere (NVE), vitreous hemorrhages (VH), preretinal hemorrhage (PRH), fibrous proliferation on the optic nerve head (FPD), and fibrous proliferation elsewhere (FPE).

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validity. Although it is recognized as the gold standard for grading the severity of diabetic retinopathy in clinical trials, its use in everyday clinical practice has not proven to be easy or practical. The grading system has more levels than may be necessary for clinical care, and the specific definitions of the levels are detailed, require comparison with standard photographs, and are difficult to remember and apply in a clinical setting. Several unpublished contemporary surveys have documented that the vast majority of physicians managing patients with diabetes do not employ the full ETDRS severity scale, because it is too complex for application in the clinical practices of retinal specialists, comprehensive ophthalmologists, endocrinologists, and primary care physicians [7].

In several countries, simplified classifications have been developed in an effort to improve both the screening of patients with diabetes and communication among caregivers. In 1993, a simplified diabetic retinopathy severity scale was developed as part of “The Initiative for the Prevention of Diabetic Eye Disease,” sponsored by the German Society of Ophthalmology (Anselm Kampik, personal communication, 2003). Another similar severity scale has been used in Japan since 1983 [8]. The organizers of a recent massive screening campaign for diabetic retinopathy in 15 Latin American and the Caribbean countries developed a customized simplified classification based on another version of the ETDRS severity scale [9], and yet another system has been employed in Australia [10]. Because each of these grading systems is unique, it is very difficult to compare data from studies using these various classification schemes.

PROPOSED INTERNATIONAL CLASSIFICATION

Despite the development of the ETDRS and additional classifications in several countries, there remained a genuine need for a single standardized practical clinical disease severity scale that could be employed around the world to facilitate communication across groups of practitioners. The severity of retinopathy may lead to different treatment strategies and recommendations in different regions because practice patterns and health care delivery systems for patients with diabetes mellitus differ around the world. Nevertheless, an optimal clinical classification system should be useful for a broad range of caregivers with varying skills and diagnostic equipment, ranging from retinal specialists with contemporary equipment to trained physician assistants using only direct ophthalmoscopes.

In September 2001, the American Academy of Ophthalmology (AAO) launched a consensus development project with the goal of developing a new clinical severity scale for diabetic retinopathy [7]. The published report [7] reviews the deliberations that led to the establishment of the scale and presents a final document upon which consensus had been achieved. The development process was sponsored by the AAO, and the AAO Board of Trustees formally approved the final classification scales in February 2003.

At the time of the initiation of this project, it was agreed that the clinical disease severity scale should be evidence-based, employing data from important clinical studies such as the ETDRS and the Wisconsin Epidemiologic Study of Diabetic

Retinopathy (WESDR) [11,12]. The severity scale was intended primarily for comprehensive ophthalmologists and primary care physicians, because these individuals evaluate most patients with diabetes. Retinal specialists were considered to be familiar with the ETDRS classification system and expected to continue using either that or their personal customized modifications.

It was hoped that “most easily visible” lesions might serve as appropriate indicators of the likelihood of progression to severe forms of retinopathy. Unfortunately, this was not the case. Prior to the large meeting, data from the ETDRS and the WESDR were re-evaluated in an effort to document the association between specific lesions and the severity of diabetic retinopathy (Ronald Klein, MD, MPH, personal communication, 2002). In evaluations performed on the ETDRS data, intraretinal microvascular anomalies (IRMA) and venous beading (VB) were very predictive of the risk of developing proliferative retinopathy, but the presence of hard exudates or soft exudates was not very predictive. The most visible signs of retinopathy, hemorrhages/microaneurysms (H/MA), did not reliably predict the risk of progression to proliferative retinopathy. WESDR data demonstrated a lack of concordance of these lesions with the presence of IRMA and VB. For right eyes with IRMA present, 41% of patients with type 1 diabetes and 42% of patients with type 2 diabetes did not have H/MA ≥ standard photograph #1 in one or more fields. For right eyes with VB present, 29% of patients with type 1 diabetes and 31% with type 2 diabetes did not have H/MA ≥ standard photograph #1 in one or more fields. The sensitivity of using H/MA greater than standard photograph #1 in one or more fields for detecting the presence of IRMA or VB was about 60%, and the specificity about 97%. Therefore, it became clear that it would be necessary to identify the specific lesions of IRMA and VB, and not rely on H/MA alone, in order to differentiate moderate from severe nonproliferative diabetic retinopathy (NPDR).

Members of the Global Diabetic Retinopathy Project Group included retina specialists, comprehensive ophthalmologists, endocrinologists, and epidemiologists [7]. A modified nominal group technique or modified Delphi technique was utilized to evaluate the level of consensus regarding this initial clinical classification [13]. A 9-point rating scale was used, with 1 being strong disagreement and 9 being strong agreement. The results were aggregated mathematically to summarize the group results. To determine agreement and disagreement, a binomial distribution was applied. Depending on the number of participants, agreement was defined to exist if more than 80% rated within a 3-point range of 1–3, 4–6, and 7–9. Disagreement was defined as a 20% rate in the 7–9 range, and at least another 20% rate in the 1–3 range. Otherwise, agreement was rated as “equivocal” or “partial” (with many participants in the 4–6 range).

The most debated items in the discussions regarding the classification scheme included: (1) addition of a level of “no apparent retinopathy”; (2) determination of the extent of neovascularization required for a classification of “proliferative retinopathy”; (3) establishment of the lowest ETDRS level indicating “severe NPDR”; and (4) development of a grading scheme for DME. The results of the final ratings regarding the first three of these are presented in Figure 2.1. There was significant disagreement for including “no apparent retinopathy” and “minimal NPDR” in a single level (Fig. 2.1A). However, there was 100% agreement regarding the

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Figure 2.1. Participant votes for portions of the Diabetic Retinopathy Disease Severity Scale Employing the modified Delphi approach. Numbers 1–3 indicate levels of disagreement. Numbers 7–9 indicate levels of agreement. There were 17 voters. (A) Votes for including “No Retinopathy” and “Mild Retinopathy” as a single level. (B) Votes for including “No Retinopathy” as a single level. (C) Votes for any proliferation to be graded as “proliferative diabetic retinopathy.” (D) Votes for including ETDRS level 47 in “Severe Retinopathy” Level. (E) Votes for not including ETDRS level 47 in “Severe Retinopathy” level.

desirability of including a single level for “no retinopathy” (Fig. 2.1B). There was also 100% agreement regarding a level for “PDR” that included all eyes with any neovascularization (Fig. 2.1C). However, a decision concerning whether or not to include ETDRS level 47 in the “severe NPDR” level was more controversial, and this ETDRS level was ultimately placed as the highest level in the “moderate NPDR” group (Figs. 2.1D and 2.1E). Regarding DME, there was significant agreement at all levels. High agreement was noted for levels of DME categorized as “apparently present” or “apparently absent” and for DME involving the fovea being designated

in a separate level (assuming that examiner training and equipment allowed the location of edema to be documented). A minor degree of disagreement was noted in two subcategories of “apparently present” DME that did not involve the fovea. This was due primarily to the reality of the difficulties involved in assigning precise levels for stages that were admittedly difficult to specify.

The diabetic retinopathy disease severity levels are listed in Table 2.2 [7]. This consists of five scales with increasing severity of retinopathy. The first level is “no apparent retinopathy,” and the absence of diabetic retinopathy is documented as a distinct first level. This designation of “no apparent retinopathy” was considered to be important in the care of patients with diabetes. Patients in particular may feel differently if they believe that they have no detectable signs of retinopathy than if definite retinopathy is detected. Although an examiner might miss one or two microaneurysms, if such a lesion is definitely detected, this indicates that retinopathy has begun, and this observation may make a difference to patients and their primary care physicians or endocrinologists.

The second level, “mild NPDR,” includes ETDRS level 20 (microaneurysms only). The risk of significant progression over several years is very low in both this and the first group.

The third level, “moderate NPDR,” includes eyes with ETDRS levels 35–47, and the risk of progression increases significantly by level 47, which is the reason that there was debate about placing level 47 in this third group (Fig. 2.1D).

The fourth level, “severe NPDR” (ETDRS stages 53 and higher), carries with it the most ominous prognosis for relatively rapid progression to PDR. The lower threshold for entry into this category was the presence of lesions consistent with the “4:2:1 rule” (Figs. 2.2–2.4). Continuing evaluations of ETDRS data have

Table 2.2. International Clinical Diabetic Retinopathy Disease Severity Scale [7]

of the world, because specific practice patterns and health care delivery systems differ from country to country.

Although this staging system is intended primarily for comprehensive ophthalmologists and others with acquired skills necessary for evaluating the retina, it is hoped that this system will also allow better communication regarding retinopathy severity among all physicians and physician extenders caring for patients with diabetes. This improved communication should lead to more effective and consistent follow-up and better patient outcomes.

Implementation of this system will rely on its dissemination to ophthalmologists and other eye care providers, and it is also important that endocrinologists, diabetologists, and primary care physicians and physicians’ assistants who care for patients with diabetes become familiar with these scales. Different localities and different structures for care will vary in approaches to implementation of care and will use different care providers and care delivery processes in managing patients with diabetes.

This scheme remains to be validated in appropriate studies. Hopefully, there will be processes to pilot test this system in a variety of local settings and to reevaluate its feasibility and utility in a variety of routine clinical environments around the world. As experience with the system is acquired, the reliability of the scales should be reevaluated. The classif ication scheme can be refined to maintain its currency as new developments occur in the management of diabetic retinopathy and DME.

ACKNOWLEDGMENTS

The author would like to thank the members of the Global Diabetic Retinopathy Project Group [7], and particularly Flora Lum, MD, for all of their efforts in developing the diabetic retinopathy disease severity scale.

REFERENCES

1.King, H, Aubert, RE, Herman, WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;1998:1414–1431.

2.Fong DS, Aiello LP, Ferris FL, et al. Diabetic retinopathy. Diabetes Care. 2004; 27:2340–2553.

3.UK Prospective Diabetes Study (UKPDS) Group. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus. Arch Ophthalmol. 2004;122:1631–1640.

4.American Academy of Ophthalmology. Diabetic Retinopathy Preferred Practice Pattern. San Francisco: American Academy of Ophthalmology; 2008.

5.Diabetic Retinopathy Study Research Group. A modification of the Airlie House classification of diabetic retinopathy. Report 7. Invest Ophthalmol Vis Sci. 1981;21:210–226.

6.Javitt JC, Aiello LP, Bassi LP, et al. Detecting and treating retinopathy in patients with type I diabetes. Savings associated with improved implementation of current guidelines. Ophthalmology. 1991;98:1565–1573.